1. Field of the Invention
This invention is directed to novel compositions suitable for use in embolizing blood vessels. In particular, this invention is directed to embolizing compositions comprising a biocompatible polymer, a biocompatible solvent and a contrasting agent. The compositions of this invention find particular utility in embolizing blood vessels in, for example, the treatment of aneurysms and in ablating diseased tissues.
This invention is also directed to methods for sterilizing male mammals generally and male humans in particular. In these methods, a composition comprising a biocompatible polymer and a biocompatible solvent is delivered to the vas deferens of the male mammal.
The biocompatible polymer is selected to be soluble in the biocompatible solvent, but insoluble in the aqueous fluid of the vas deferens. The biocompatible solvent is miscible or soluble in this aqueous fluid and, upon contact with this fluid, the biocompatible solvent quickly diffuses away whereupon the biocompatible polymer precipitates to form an occlusion in the vas deferens which blocks the passage of spermatic fluid.
A significant advantage of the methods of this invention is that the sterilization can be reversed merely by dissolving the biocompatible polymer forming the occlusion with the biocompatible solvent.
References
    1 Mandai, et al., “Direct Thrombosis of Aneurysms with Cellulose Acetate Polymer”, J. Neurosurg., 22:497-500 (1992)    2 Kinugasa, et al., “Direct Thrombosis of Aneurysms with Cellulose Acetate Polymer”, J. Neurosurg., 22:501-507 (1992)    3 Greff, et al., U. S. patent application Ser. No. 08/508,248, for “Cellulose Diacetate Compositions for Use in Embolizing Blood Vessels, filed Jul. 27, 1995.    4 Greff, et al., U.S. patent application Ser. No. 08/507,863, for “Novel Compositions for Use in Embolizing Blood Vessels”, filed Jul. 27, 1995.    5 Evans, et al., U.S. patent application Ser. No. 08/655,987 for “Methods for the Reversible Sterilization of Male Mammals, filed concurrently herewith as Attorney Docket No. 018413-007    6 Evans, et al., U.S. patent application Ser. No. 08/656,394 for “Methods for the Reversible Sterilization of Female Mammals, filed concurrently herewith as Attorney Docket No. 018413-014    7 Goldsmith, et al., “Transcutaneous Procedures for Male Sterilization,” Adv. Contracept., 1:355-361 (1985).    8 Chvapil, et al., “Occlusion of the Vas Deferens in Dogs with a Biocompatible Hydrogel Solution,” J. Reproductive Med., 35(9):905-910 (1990).    9 Zhao Sheng-cai, “Vas Deferens Occlusion by Percutaneous Injection of Polyurethane Elastomer Plugs: Clinical Experience and Reversibility,” Contraception, 41:453-459 (1990).    10 Sethi, et al., “Histological Changes in the Vas Deferens of Rats After Injection of a New Male Antifertility Agent ‘SMA’ and Its Reversibility,” Contraception, 41:333-339 (1990).    11 Guha, et at., “Time-Controlled Injectable Occlusion of the Vas Deferens,” contraception, 41:323-331(1990).    12 Sethi, et al., “Safety Evaluation of a Male Injectable Antifertility Agent, Styrene Maleic Anhydride, in Rats,” Contraception, 2:217-227 (1989).    13 Kinugasa, et al., “Direct Thrombosis of Aneurysms with Cellulose Acetate Polymer”, J. Neurosurg., 77:501-507 (1992).    14 Kinugasa, et al., “Early Treatment of Subarachnoid Hemorrhage After Preventing Rerupture of an Aneurysm”, J. Neurosurg., 34-41 (1995).    15 Kinugasa, et al., “Prophylactic Thrombosis to Prevent New Bleeding and to Delay Aneurysm Surgery”, Neurosurg., 661 (1995).    16 Taki, et al., “Selection and Combination of Various Endovascular Techniques in the Treatment of Giant Aneurysms”, J. Neurosurg., 22:37-42 (1992).    17 Rabinowitz, et al., U.S. Pat. No. 3,527,224, for “Method of Surgically Bonding Tissue Together”, issued Sep. 8, 1970.    18 Hawkins, et al., U.S. Pat. No. 3,591,676, for “Surgical Adhesive Compositions”, issued Jul. 6, 1971.    19 Stoy, et al., U.S. Pat. No. 4,631,188, for “Injectable Physiologically-Acceptable Polymeric Compositions”, issued Dec. 23, 1986    20 Dewitt, “Surgery of the Male Genital Tract”, in Family Medicine Principles and Practice, 4th Edition, Taylor, Editor, pp. 778-780 (1994)    21 Park, et al., “New Polymers for Therapeutic Embolization”, Poster #47, Meeting of Radiological Society of North America (1993)
All of the above references are herein incorporated by reference in their entirety to the same extent as if each individual reference was specifically and individually indicated to be incorporated herein by reference in its entirety.
2. State of the Art
It is desirable in many clinical situations to embolize blood vessels to prevent/control bleeding (e.g., organ bleeding, gastrointestinal bleeding, vascular bleeding, bleeding associated with an aneurysm) or to ablate diseased tissue (e.g., tumors, etc.). Embolization of blood vessels has heretofore employed certain polymer compositions and particulates, e.g., silicone, metallic coils, sclerosing materials and the like. Because of their ease in delivery, water insoluble non-biodegradable polymers such as cellulose acetate1,2,3 or ethylene vinyl alcohol4 dissolved in, for example, DMSO have been employed to embolize blood vessels. These compositions are delivered to the vascular site to be embolized by, for example, a catheter or a syringe. Typically, these compositions will comprise a contrast agent to facilitate guidance of the catheter or syringe to the vascular site as well as the placement of the polymer precipitate which embolizes the blood vessel. Upon contact with the aqueous blood environment at this vascular site, the DMSO dissipates away from the insoluble polymer which results in polymer precipitation and embolization of the blood vessel.
In addition to use in embolizing blood vessels, these compositions can also be employed in the reversible sterilization of mammalian males and females.5,6 
Vasectomy has been recognized as one of the safest. simplest. and most effective forms of male sterilization.7,8,20 As normally practiced, this procedure involves a skin incision and some dissection of the vas deferens.9 Notwithstanding the safety and effectiveness of a vasectomy, such sterilization is difficult to reverse and, at best, only a fraction of vasectomies can be successfully reversed. Accordingly, research has been ongoing to develop new methods of male sterilization for over 30 years.
There are two primary reasons for the continued research into male sterilization. One is that a vasectomy requires a skin incision which is undesirable to most men. The other reason is the lack of certain reversibility.9 
Several attempts have been made to develop a non-surgical and reversible method of male sterilization.10,11,12 One such attempt involves the injection of an antifertility agent into the vas deferens of rats and monkeys.10 The antifertility agent comprises styrene maleic anhydride (SMA) dissolved in dimethylsulfoxide (DMSO). When injected into the vas deferens, the SMA occludes the vas deferens lumen as well as inhibits the fertilizing ability of spermatozoa by virtue of its pH-lowering effect. This sterilization method can be reversed by flushing the SMA out with the solvent DMSO.10 
Still another attempt involves the injection of a polymeric hydrogel solution in a suitable solvent such as DMSO into the vas deferens.19 Upon injection into the vas deferens, the polymeric composition slowly coagulates into a spongy polymer structure which takes up water to form a hydrogel composition.
In carrying out such non-surgical procedures, various tests have been employed to verify that the antifertility agent will be or has been injected properly into the vas deferens. One such test is to inject air into a finger-occluded distal section of the vas to see if an air bubble forms.9 If an air bubble does form, the needle tip is properly placed in the lumen. Another test involves injecting different color dyes into each of the contralateral vas.9 After the procedure is completed, the subject is asked to urinate. If the color of the urine is a mixture of dyes, then the bilateral injections are successful. However, if the urine color is normal or is one color of the dye or the other, then the procedure is unsuccessful.
It is apparent that such methods for determining whether the antifertility agent is properly injected into the lumen or whether the procedure as a whole is successful have drawbacks. For example, in the air bubble test, if the lumen does not inflate when air is injected, then some skillful maneuvering of the needle tip will be required in order to properly deliver the antifertility agent. With the dye method, success or failure of the procedure cannot be determined until after it has been completed.
In view of the above drawbacks, a need continues to exist in the art for an easy, reliable, and dependable method of sterilizing male mammals.
Still further, the polymeric compositions of this invention do not include compositions which form a hydrogel in situ because, as noted in Stoy.19 such compositions can cause osmotic shock to neighboring tissue. Furthermore, the coagulation process is rather slow for such hydrogels with only a sponganeous polymer forming in situ. This slow coagulation process could lend itself to migration of at least some of the polymer from the intended site of application prior to formation of the sponganeous polymer. Moreover, at least conceptually, a sponganeous polymer could be open to migration of a small percentage of active sperm through the polymer and into the ejaculate of the male mammal.